Fusion of epithelial ridges is important during development of the neural tube, secondary palate, nasal processes, optic cup, penis and heart. Abnormalities in the fusion process may be responsible for specific malformations related to the region affected, i.e. exencephaly, cleft palate and lip, coloboma iridis, hypospadius etc. The purpose of this study will be to examine factors implicated as being essential for epithelial fusion -formation of surface coats, cell death, and development of epithelial ridges - which may also be involved in mechanisms of teratogenesis. The study will also determine the efficacy of using culture techniques, capable of maintaining mouse embryos in vitro during the organogenic (teratogenic) period, as a means of assessing and determining effects of teratogens. Neural tube closure in the mouse will be used as the model system to investigate the importance of each parameter and in vivo and in vitro (whole embryo culture) techniques will be employed: Surface coats will be examined by light and electron microscopy for time, amount, and location of deposition. Synthesis of these coats will be monitored using labelled precursors. The importance of surface coats during fusion will be determined using inhibitors of surface coat formation and deposition. The role of cell death will be investigated in several ways: First, normal cell death will be examined with light and electron microscopy to determine location, amounts, and types of necrosis. Second, cytotoxic agents will be used to determine the effects of increased necrotic activity on fusion. Agents which prevent cell death will also be used to examine effects on fusion when cell necrosis is inhibited. The importance of formation of epithelial ridges wll be examined in two ways: First cytotoxic agents will be used to decrease cell numbers and prevent ridge elevation. Second, inhibitors of microtubule and microfilament formation will be employed to prevent changes in cell shape, which are related to ridge formation. Examining and manipulating these events will provide information necessary to understanding epithelial fusion and congenital malformations (in this instance exencephaly and spina bifida) which may be related to interference of fusion processes.